An Unexpected pH Effect on the Stability of Moexipril Lyophilized Powder

摘要: Because of the limited stability moexipril (RS-10085; 1) in aqueous solution, lyophilized parenteral formulations were evaluated as a function pH this study. In general, powder 1 showed about two orders magnitude less reactivity at 50°C than solution values below 3 or above 6. At 5.1, however, had maximum reactivity, with rate actually comparable to that observed solution. When distribution major products, diketopiperazine (DKP) 2 and ester hydrolysis analogue 3, was compared kinetics pH, it clear removal water via lyophilization suppressed spontaneous k1 cyclization process, k3 specific base-catalyzed k4 process. The overall k2 not affected by lyophilization. latter result is accounted for increased equilibrium constant formation tetrahedral intermediate, To, This study demonstrates data can be used predicting form.